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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Mervenur Yavuz and Turan Demircan*

DOI: 10.2174/1871520623666221125115542

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The Effect of Hydroquinidine on Proliferation and Apoptosis of TMZ-sensitive and -resistant GBM Cells

Page: [938 - 952] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Background: Glioblastoma multiforme (GBM) is a lethal form of central nervous system cancer with a lack of efficient therapy options. Aggressiveness and invasiveness of the GBM result in poor prognosis and low overall survival. Therefore, the necessity to develop new anti-carcinogenic agents in GBM treatment is still a priority for researchers. Ion channels are one of the primary regulators of physiological homeostasis with additional critical roles in many essential biological processes related to cancer, such as invasion and metastasis. A multi-channel blocker, hydroquinidine (HQ), is currently in use to treat short-QT and Brugada arrhythmia syndromes.

Objective: The objective of the study was to examine the alterations in survival, clonogenicity, migration, tumorigenicity, proliferation, apoptosis, and gene expression profile of temozolomide (TMZ)-sensitive and TMZ-resistant GBM cells upon HQ treatment.

Methods: The possible anti-neoplastic activity of HQ on GBM cells was investigated by several widely applied cell culture methods. The IC50 values were determined using the MTT assay. Upon HQ treatment, the clonogenicity and migration capacity of cells were evaluated via colony-formation and wound healing assay, respectively. For antiproliferative and apoptotic effects, EdU and CFSE, and Annexin-V labeling were applied. Tumorigenicity level was depicted by employing soft agar assay. The expression level of multiple genes functioning in the cell cycle and apoptosis- related processes was checked utilizing qPCR.

Results: A significant anti-carcinogenic effect of HQ on TMZ-sensitive and -resistant GBM cells characterized by the increased apoptosis and decreased proliferation rate was revealed due to the altered gene expression profile related to cell cycle and cell death.

Conclusion: In this study, the anti-carcinogenic effect of HQ has been demonstrated for the first time. Our data suggest the possible utilization of HQ to suppress the growth of GBM cells. Further studies on GBM-bearing animal models are required to assess its therapeutic potential in GBM treatment.

Graphical Abstract

[1]
Batash, R.; Asna, N.; Schaffer, P.; Francis, N.; Schaffer, M. Glioblastoma multiforme, diagnosis and treatment; recent literature review. Curr. Med. Chem., 2017, 24(27), 3002-3009.
[http://dx.doi.org/10.2174/0929867324666170516123206] [PMID: 28521700]
[2]
Gilbert, M.R.; Wang, M.; Aldape, K.D.; Stupp, R.; Hegi, M.E.; Jaeckle, K.A.; Armstrong, T.S.; Wefel, J.S.; Won, M.; Blumenthal, D.T.; Mahajan, A.; Schultz, C.J.; Erridge, S.; Baumert, B.; Hopkins, K.I.; Tzuk-Shina, T.; Brown, P.D.; Chakravarti, A.; Curran, W.J., Jr; Mehta, M.P. Dose-dense temozolomide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J. Clin. Oncol., 2013, 31(32), 4085-4091.
[http://dx.doi.org/10.1200/JCO.2013.49.6968] [PMID: 24101040]
[3]
Davis, M. Glioblastoma: Overview of disease and treatment. Clin. J. Oncol. Nurs., 2016, 20(5)(Suppl.), S2-S8.
[http://dx.doi.org/10.1188/16.CJON.S1.2-8] [PMID: 27668386]
[4]
Paw, I.; Carpenter, R.C.; Watabe, K.; Debinski, W.; Lo, H.W. Mechanisms regulating glioma invasion. Cancer Lett., 2015, 362(1), 1-7.
[http://dx.doi.org/10.1016/j.canlet.2015.03.015] [PMID: 25796440]
[5]
Mann, J.; Ramakrishna, R.; Magge, R.; Wernicke, A.G. Advances in radiotherapy for glioblastoma. Front. Neurol., 2018, 8, 748.
[http://dx.doi.org/10.3389/fneur.2017.00748] [PMID: 29379468]
[6]
Roos, W.P.; Batista, L F Z.; Naumann, S.C.; Wick, W.; Weller, M.; Menck, C F M.; Kaina, B. Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine. Oncogene, 2007, 26(2), 186-197.
[http://dx.doi.org/10.1038/sj.onc.1209785] [PMID: 16819506]
[7]
Schreck, K.C.; Grossman, S.A. Role of temozolomide in the treatment of cancers involving the central nervous system. Oncology, 2018, 32(11), 555-560, 569.
[PMID: 30474103]
[8]
Yung, W.K.A.; Prados, M.D.; Yaya-Tur, R.; Rosenfeld, S.S.; Brada, M.; Friedman, H.S.; Albright, R.; Olson, J.; Chang, S.M.; O’Neill, A.M.; Friedman, A.H.; Bruner, J.; Yue, N.; Dugan, M.; Zaknoen, S.; Levin, V.A. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J. Clin. Oncol., 1999, 17(9), 2762-2771.
[http://dx.doi.org/10.1200/JCO.1999.17.9.2762] [PMID: 10561351]
[9]
Portnow, J.; Badie, B.; Chen, M.; Liu, A.; Blanchard, S.; Synold, T.W. The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: Potential implications for the current approach to chemoradiation. Clin. Cancer Res., 2009, 15(22), 7092-7098.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1349] [PMID: 19861433]
[10]
Karachi, A.; Dastmalchi, F.; Mitchell, D.A.; Rahman, M. Temozolomide for immunomodulation in the treatment of glioblastoma. Neuro-oncol., 2018, 20(12), 1566-1572.
[http://dx.doi.org/10.1093/neuonc/noy072] [PMID: 29733389]
[11]
van Nifterik, K.A.; van den Berg, J.; van der Meide, W.F.; Ameziane, N.; Wedekind, L.E.; Steenbergen, R.D.M.; Leenstra, S.; Lafleur, M.V.M.; Slotman, B.J.; Stalpers, L.J.A.; Sminia, P. Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide. Br. J. Cancer, 2010, 103(1), 29-35.
[http://dx.doi.org/10.1038/sj.bjc.6605712] [PMID: 20517307]
[12]
Pushpakom, S.; Iorio, F.; Eyers, P.A.; Escott, K.J.; Hopper, S.; Wells, A.; Doig, A.; Guilliams, T.; Latimer, J.; McNamee, C.; Norris, A.; Sanseau, P.; Cavalla, D.; Pirmohamed, M. Drug repurposing: Progress, challenges and recommendations. Nat. Rev. Drug Discov., 2019, 18(1), 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[13]
Yu, F.H.; Yarov-Yarovoy, V.; Gutman, G.A.; Catterall, W.A. Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol. Rev., 2005, 57(4), 387-395.
[http://dx.doi.org/10.1124/pr.57.4.13] [PMID: 16382097]
[14]
Griffin, M.; Khan, R.; Basu, S.; Smith, S. Ion channels as therapeutic targets in high grade gliomas. Cancers, 2020, 12(10), 3068.
[http://dx.doi.org/10.3390/cancers12103068] [PMID: 33096667]
[15]
Kunzelmann, K. Ion channels and cancer. J. Membr. Biol., 2005, 205(3), 159-173.
[http://dx.doi.org/10.1007/s00232-005-0781-4] [PMID: 16362504]
[16]
Hoffmann, E.K.; Lambert, I.H. Ion channels and transporters in the development of drug resistance in cancer cells. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2014, 369(1638)20130109
[http://dx.doi.org/10.1098/rstb.2013.0109] [PMID: 24493757]
[17]
Lang, F.; Stournaras, C. Ion channels in cancer: future perspectives and clinical potential. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2014, 369(1638)20130108
[http://dx.doi.org/10.1098/rstb.2013.0108] [PMID: 24493756]
[18]
Crottès, D.; Jan, L.Y. The multifaceted role of TMEM16A in cancer. Cell Calcium, 2019, 82102050
[http://dx.doi.org/10.1016/j.ceca.2019.06.004] [PMID: 31279157]
[19]
Arcangeli, A. Ion channels and transporters in cancer. 3. Ion channels in the tumor cell-microenvironment cross talk. Am. J. Physiol. Cell Physiol., 2011, 301(4), C762-C771.
[http://dx.doi.org/10.1152/ajpcell.00113.2011] [PMID: 21562309]
[20]
Panyi, G.; Beeton, C.; Felipe, A. Ion channels and anti-cancer immunity. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2014, 369(1638)20130106
[http://dx.doi.org/10.1098/rstb.2013.0106] [PMID: 24493754]
[21]
Monje, M.; Borniger, J.C.; D’Silva, N.J.; Deneen, B.; Dirks, P.B.; Fattahi, F.; Frenette, P.S.; Garzia, L.; Gutmann, D.H.; Hanahan, D.; Hervey-Jumper, S.L.; Hondermarck, H.; Hurov, J.B.; Kepecs, A.; Knox, S.M.; Lloyd, A.C.; Magnon, C.; Saloman, J.L.; Segal, R.A.; Sloan, E.K.; Sun, X.; Taylor, M.D.; Tracey, K.J.; Trotman, L.C.; Tuveson, D.A.; Wang, T.C.; White, R.A.; Winkler, F. Roadmap for the emerging field of cancer neuroscience. Cell, 2020, 181(2), 219-222.
[http://dx.doi.org/10.1016/j.cell.2020.03.034] [PMID: 32302564]
[22]
Sales, T.T.; Resende, F.F.B.; Chaves, N.L.; Titze-De-Almeida, S.S.; Báo, S.N.; Brettas, M.L.; Titze-De-Almeida, R. Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide. Oncol. Lett., 2016, 12(4), 2581-2589.
[http://dx.doi.org/10.3892/ol.2016.4992] [PMID: 27698831]
[23]
Martínez, R.; Stühmer, W.; Martin, S.; Schell, J.; Reichmann, A.; Rohde, V.; Pardo, L. Analysis of the expression of Kv10.1 potassium channel in patients with brain metastases and glioblastoma multiforme: impact on survival. BMC Cancer, 2015, 15(1), 839.
[http://dx.doi.org/10.1186/s12885-015-1848-y] [PMID: 26530050]
[24]
Zhang, Y.; Zhou, L.; Zhang, J.; Zhang, L.; Yan, X.; Su, J. Suppression of chloride voltage gated channel 3 expression increases sensitivity of human glioma U251 cells to cisplatin through lysosomal dysfunction. Oncol. Lett., 2018, 16(1), 835-842.
[http://dx.doi.org/10.3892/ol.2018.8736] [PMID: 29963152]
[25]
Huo, J.F.; Chen, X.B. P2X4R silence suppresses glioma cell growth through BDNF/TrkB/ATF4 signaling pathway. J. Cell. Biochem., 2019, 120(4), 6322-6329.
[http://dx.doi.org/10.1002/jcb.27919] [PMID: 30362154]
[26]
Setti, M.; Savalli, N.; Osti, D.; Richichi, C.; Angelini, M.; Brescia, P.; Fornasari, L.; Carro, M.S.; Mazzanti, M.; Pelicci, G. Functional role of CLIC1 ion channel in glioblastoma-derived stem/progenitor cells. J. Natl. Cancer Inst., 2013, 105(21), 1644-1655.
[http://dx.doi.org/10.1093/jnci/djt278] [PMID: 24115360]
[27]
Barbieri, F.; Würth, R.; Pattarozzi, A.; Verduci, I.; Mazzola, C.; Cattaneo, M.G.; Tonelli, M.; Solari, A.; Bajetto, A.; Daga, A.; Vicentini, L.M.; Mazzanti, M.; Florio, T. Inhibition of chloride intracellular channel 1 (CLIC1) as biguanide class-effect to impair human glioblastoma stem cell viability. Front. Pharmacol., 2018, 9, 899.
[http://dx.doi.org/10.3389/fphar.2018.00899] [PMID: 30186163]
[28]
Sontheimer, H. An unexpected role for ion channels in brain tumor metastasis. Exp. Biol. Med., 2008, 233(7), 779-791.
[http://dx.doi.org/10.3181/0711-MR-308] [PMID: 18445774]
[29]
Scragg, A.H.; Allan, E.J. The potential of plant cell culture for the production of quinine. Acta Leiden., 1987, 55, 45-51.
[PMID: 3321839]
[30]
Achan, J.; Talisuna, A.O.; Erhart, A.; Yeka, A.; Tibenderana, J.K.; Baliraine, F.N.; Rosenthal, P.J.; D’Alessandro, U. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar. J., 2011, 10(1), 144.
[http://dx.doi.org/10.1186/1475-2875-10-144] [PMID: 21609473]
[31]
Christensen, S.B. Natural products that changed society. Biomedicines, 2021, 9(5), 472.
[http://dx.doi.org/10.3390/biomedicines9050472] [PMID: 33925870]
[32]
Zou, L.; Xue, Y.; Jones, M.; Heinbockel, T.; Ying, M.; Zhan, X. The effects of quinine on neurophysiological properties of dopaminergic neurons. Neurotox. Res., 2018, 34(1), 62-73.
[http://dx.doi.org/10.1007/s12640-017-9855-1] [PMID: 29285614]
[33]
Yan, M.; Fan, P.; Shi, Y.; Feng, L.; Wang, J.; Zhan, G.; Li, B. Stereoselective blockage of quinidine and quinine in the hERG channel and the effect of their rescue potency on drug-induced hERG trafficking defect. Int. J. Mol. Sci., 2016, 17(10), 1648.
[http://dx.doi.org/10.3390/ijms17101648] [PMID: 27690007]
[34]
El-Battrawy, I.; Besler, J.; Li, X.; Lan, H.; Zhao, Z.; Liebe, V.; Schimpf, R.; Lang, S.; Wolpert, C.; Zhou, X.; Akin, I.; Borggrefe, M. Impact of antiarrhythmic drugs on the outcome of short QT syndrome. Front. Pharmacol., 2019, 10, 771.
[http://dx.doi.org/10.3389/fphar.2019.00771] [PMID: 31427960]
[35]
Mercer, B.N.; Begg, G.A.; Page, S.P.; Bennett, C.P.; Tayebjee, M.H.; Mahida, S. Early repolarization syndrome; mechanistic theories and clinical correlates. Front. Physiol., 2016, 7, 266.
[http://dx.doi.org/10.3389/fphys.2016.00266] [PMID: 27445855]
[36]
Perrin, T.; Guieu, R.; Koutbi, L.; Franceschi, F.; Hourdain, J.; Brignole, M.; Deharo, J.C. Theophylline as an adjunct to control malignant ventricular arrhythmia associated with early repolarization. Pacing Clin. Electrophysiol., 2018, 41(5), 444-446.
[http://dx.doi.org/10.1111/pace.13240] [PMID: 29148059]
[37]
Mazzanti, A.; Maragna, R.; Vacanti, G.; Kostopoulou, A.; Marino, M.; Monteforte, N.; Bloise, R.; Underwood, K.; Tibollo, V.; Pagan, E.; Napolitano, C.; Bellazzi, R.; Bagnardi, V.; Priori, S.G. Hydroquinidine prevents life-threatening arrhythmic events in patients with short QT syndrome. J. Am. Coll. Cardiol., 2017, 70(24), 3010-3015.
[http://dx.doi.org/10.1016/j.jacc.2017.10.025] [PMID: 29241489]
[38]
Hermida, J.S.; Denjoy, I.; Clerc, J.; Extramiana, F.; Jarry, G.; Milliez, P.; Guicheney, P.; Di Fusco, S.; Rey, J.L.; Cauchemez, B.; Leenhardt, A. Hydroquinidine therapy in Brugada syndrome. J. Am. Coll. Cardiol., 2004, 43(10), 1853-1860.
[http://dx.doi.org/10.1016/j.jacc.2003.12.046] [PMID: 15145111]
[39]
Krishnaveni, M.; Suresh, K.; Arunkumar, R. Anti-proliferative and apoptotic effects of quinine in human Hep-2 laryngeal cancer and KB oral cancer cell. Bangladesh J. Pharmacol., 2016, 11(3), 593-602.
[http://dx.doi.org/10.3329/bjp.v11i3.26961]
[40]
Liu, W.; Qi, Y.; Liu, L.; Tang, Y.; Wei, J.; Zhou, L. Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor-associated factor 6-AKT interaction. Mol. Med. Rep., 2016, 14(3), 2171-2179.
[http://dx.doi.org/10.3892/mmr.2016.5492] [PMID: 27430155]
[41]
Sibai, M.; Parlayan, C.; Tuğlu, P.; Öztürk, G.; Demircan, T. Integrative analysis of axolotl gene expression data from regenerative and wound healing limb tissues. Sci. Rep., 2019, 9(1), 20280.
[http://dx.doi.org/10.1038/s41598-019-56829-6] [PMID: 31889169]
[42]
Demircan, T.; İlhan, A.E.; Ovezmyradov, G.; Öztürk, G.; Yıldırım, S. Longitudinal 16S rRNA data derived from limb regenerative tissue samples of axolotl Ambystoma mexicanum. Sci. Data, 2019, 6(1), 70.
[http://dx.doi.org/10.1038/s41597-019-0077-7] [PMID: 31123261]
[43]
Demircan, T.; Yavuz, M.; Kaya, E.; Akgül, S.; Altuntaş, E. Cellular and molecular comparison of glioblastoma multiform cell lines. Cureus, 2021, 13(6)e16043
[http://dx.doi.org/10.7759/cureus.16043] [PMID: 34345539]
[44]
Sofroniew, M.V.; Vinters, H.V. Astrocytes: biology and pathology. Acta Neuropathol., 2010, 119(1), 7-35.
[http://dx.doi.org/10.1007/s00401-009-0619-8] [PMID: 20012068]
[45]
Lin, D.; Wang, M.; Chen, Y.; Gong, J.; Chen, L.; Shi, X.; Lan, F.; Chen, Z.; Xiong, T.; Sun, H.; Wan, S. Trends in intracranial glioma incidence and mortality in the United States, 1975-2018. Front. Oncol., 2021, 11748061
[http://dx.doi.org/10.3389/fonc.2021.748061] [PMID: 34790574]
[46]
Akhtar, N.; Pradhan, N.; Barik, G.K.; Chatterjee, S.; Ghosh, S.; Saha, A.; Satpati, P.; Bhattacharyya, A.; Santra, M.K.; Manna, D. Quinine-based semisynthetic ion transporters with potential antiproliferative activities. ACS Appl. Mater. Interfaces, 2020, 12(23), 25521-25533.
[http://dx.doi.org/10.1021/acsami.0c01259] [PMID: 32425038]
[47]
El-Mesery, M.; Seher, A.; El-Shafey, M.; El-Dosoky, M.; Badria, F.A. Repurposing of quinoline alkaloids identifies their ability to enhance doxorubicin‐induced sub‐G0/G1 phase cell cycle arrest and apoptosis in cervical and hepatocellular carcinoma cells. Biotechnol. Appl. Biochem., 2021, 68(4), 832-840.
[http://dx.doi.org/10.1002/bab.1999] [PMID: 32757395]
[48]
Melkoumian, Z.K.; Martirosyan, A.R.; Strobl, J.S. Myc protein is differentially sensitive to quinidine in tumorversus immortalized breast epithelial cell lines. Int. J. Cancer, 2002, 102(1), 60-69.
[http://dx.doi.org/10.1002/ijc.10648] [PMID: 12353235]
[49]
Solh, M.; Appel, J.; Dubay, L.; Lobocki, C.; Mittal, V. Quinine enhances the apoptotic and antiproliferative effects of seocalcitol in breast cancer cell lines. Cancer Res., 2008, 68, 4028-4028.
[50]
Weiger, T.M.; Colombatto, S.; Kainz, V.; Heidegger, W.; Grillo, M.A.; Hermann, A. Potassium channel blockers quinidine and caesium halt cell proliferation in C6 glioma cells via a polyamine-dependent mechanism. Biochem. Soc. Trans., 2007, 35(2), 391-395.
[http://dx.doi.org/10.1042/BST0350391] [PMID: 17371284]
[51]
Utermark, T.; Alekov, A.; Lerche, H.; Abramowski, V.; Giovannini, M.; Hanemann, C.O. Quinidine impairs proliferation of neurofibromatosis type 2-deficient human malignant mesothelioma cells. Cancer, 2003, 97(8), 1955-1962.
[http://dx.doi.org/10.1002/cncr.11275] [PMID: 12673723]
[52]
Ru, Q.; Tian, X.; Pi, M.S.; Chen, L.; Yue, K.; Xiong, Q.; Ma, B.M.; Li, C.Y. Voltage-gated K+ channel blocker quinidine inhibits proliferation and induces apoptosis by regulating expression of microRNAs in human glioma U87-MG cells. Int. J. Oncol., 2015, 46(2), 833-840.
[http://dx.doi.org/10.3892/ijo.2014.2777] [PMID: 25420507]
[53]
Comes, N.; Serrano-Albarrás, A.; Capera, J.; Serrano-Novillo, C.; Condom, E.; Ramón y Cajal, S.; Ferreres, J.C.; Felipe, A. Involvement of potassium channels in the progression of cancer to a more malignant phenotype. Biochim. Biophys. Acta Biomembr., 2015, 1848(10), 2477-2492.
[http://dx.doi.org/10.1016/j.bbamem.2014.12.008] [PMID: 25517985]
[54]
Turner, K.L.; Sontheimer, H. Cl − and K + channels and their role in primary brain tumour biology. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2014, 369(1638)20130095
[http://dx.doi.org/10.1098/rstb.2013.0095] [PMID: 24493743]
[55]
Zhang, Y.; Wang, H.; Qian, Z.; Feng, B.; Zhao, X.; Jiang, X.; Tao, J. Low-voltage-activated T-type Ca2+ channel inhibitors as new tools in the treatment of glioblastoma: the role of endostatin. Pflugers Arch., 2014, 466(4), 811-818.
[http://dx.doi.org/10.1007/s00424-013-1427-5] [PMID: 24407946]
[56]
Joshi, A.D.; Parsons, D.W.; Velculescu, V.E.; Riggins, G.J. Sodium ion channel mutations in glioblastoma patients correlate with shorter survival. Mol. Cancer, 2011, 10(1), 17.
[http://dx.doi.org/10.1186/1476-4598-10-17] [PMID: 21314958]
[57]
Chen, D.; Song, M.; Mohamad, O.; Yu, S.P. Inhibition of Na+/K+-ATPase induces hybrid cell death and enhanced sensitivity to chemotherapy in human glioblastoma cells. BMC Cancer, 2014, 14(1), 716.
[http://dx.doi.org/10.1186/1471-2407-14-716] [PMID: 25255962]
[58]
Xing, D.; Wang, J.; Ou, S.; Wang, Y.; Qiu, B.; Ding, D.; Guo, F.; Gao, Q. Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells. Oncol. Rep., 2014, 31(6), 2692-2700.
[http://dx.doi.org/10.3892/or.2014.3143] [PMID: 24756536]
[59]
Dinevska, M.; Gazibegovic, N.; Morokoff, A.P.; Kaye, A.H.; Drummond, K.J.; Mantamadiotis, T.; Stylli, S.S. Inhibition of radiation and temozolomide-induced glioblastoma invadopodia activity using ion channel drugs. Cancers, 2020, 12(10), 2888.
[http://dx.doi.org/10.3390/cancers12102888] [PMID: 33050088]
[60]
Lobastova, L.; Kraus, D.; Glassmann, A.; Khan, D.; Steinhäuser, C.; Wolff, C.; Veit, N.; Winter, J.; Probstmeier, R. Collective cell migration of thyroid carcinoma cells: a beneficial ability to override unfavourable substrates. Cell. Oncol., 2017, 40(1), 63-76.
[http://dx.doi.org/10.1007/s13402-016-0305-5] [PMID: 27826898]
[61]
Tamura, R.E.; de Vasconcellos, J.F.; Sarkar, D.; Libermann, T.A.; Fisher, P.B.; Zerbini, L.F. GADD45 proteins: central players in tumorigenesis. Curr. Mol. Med., 2012, 12(5), 634-651.
[http://dx.doi.org/10.2174/156652412800619978] [PMID: 22515981]
[62]
Al Bitar, S.; Gali-Muhtasib, H. The role of the cyclin dependent kinase inhibitor p21cip1/waf1 in targeting cancer: molecular mechanisms and novel therapeutics. Cancers, 2019, 11(10), 1475.
[http://dx.doi.org/10.3390/cancers11101475] [PMID: 31575057]
[63]
Aleem, E.; Kiyokawa, H.; Kaldis, P. Cdc2–cyclin E complexes regulate the G1/S phase transition. Nat. Cell Biol., 2005, 7(8), 831-836.
[http://dx.doi.org/10.1038/ncb1284] [PMID: 16007079]
[64]
Zhou, Q.; McCracken, M.A.; Strobl, J.S. Control of mammary tumor cell growth in vitro by novel cell differentiation and apoptosis agents. Breast Cancer Res. Treat., 2002, 75(2), 107-117.
[http://dx.doi.org/10.1023/A:1019698807564] [PMID: 12243503]
[65]
Finucane, D.M.; Bossy-Wetzel, E.; Waterhouse, N.J.; Cotter, T.G.; Green, D.R. Bax-induced caspase activation and apoptosis via cytochrome c release from mitochondria is inhibitable by Bcl-xL. J. Biol. Chem., 1999, 274(4), 2225-2233.
[http://dx.doi.org/10.1074/jbc.274.4.2225] [PMID: 9890985]
[66]
Yu, J.; Zhang, L. PUMA, a potent killer with or without p53. Oncogene, 2008, 27(S1)(Suppl. 1), S71-S83.
[http://dx.doi.org/10.1038/onc.2009.45] [PMID: 19641508]
[67]
Fukuda, S.; Pelus, L.M. Survivin, a cancer target with an emerging role in normal adult tissues. Mol. Cancer Ther., 2006, 5(5), 1087-1098.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0375] [PMID: 16731740]
[68]
Qie, S.; Diehl, J.A. Cyclin D1, cancer progression, and opportunities in cancer treatment. J. Mol. Med., 2016, 94(12), 1313-1326.
[http://dx.doi.org/10.1007/s00109-016-1475-3] [PMID: 27695879]
[69]
Honda, R.; Lowe, E.D.; Dubinina, E.; Skamnaki, V.; Cook, A.; Brown, N.R.; Johnson, L.N. The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles. EMBO J., 2005, 24(3), 452-463.
[http://dx.doi.org/10.1038/sj.emboj.7600554] [PMID: 15660127]
[70]
Huang, H. matrix metalloproteinase-9 (mmp-9) as a cancer biomarker and mmp-9 biosensors: Recent advances. Sensors, 2018, 18(10), 3249.
[http://dx.doi.org/10.3390/s18103249] [PMID: 30262739]